The nature and control of the immune response to modified-self cell surface antigens will be investigated as a model for the anti-autochthonous tumor response. Our approach is to use syngeneic cellular carriers, and their isolated membrane antigens, as tolerogenic carriers capable of inducing B-cell-unresponsiveness. We will analyze the nature of the optimal carriers and the mechanism of tolerance in this system as a prelude to using tumor specific antigens (TSAs) as haptens. Furthermore, since hapten-modified syngeneic cells induce a cytotoxic T-cell response to haptenated H-2 (in the mouse), we will study the parameters of this response, its involvements (if any) in the suppression of the B cell response, and possible ways of augmenting the generation of cytotoxic T cells. This will be primarily effected by the associative recognition of allogeneic histocompatibility antigens on the modified cells. Finally, we will apply the knowledge gained in these areas to the regulation of the immune response to TSAs and the immunotherapy of human neoplasia.